Electrophysiologic Study Indications And Evaluation

Earn CME/CE in your profession:


Continuing Education Activity

An electrophysiology study is performed for the identification of arrhythmias and risk stratification of patients at risk of sudden cardiac death. Measurement of baseline intervals, incremental and decremental pacing of the atria and ventricles with an additional pharmacologic challenge, mapping, and catheter ablation are components of an electrophysiology study. This activity highlights the use of electrophysiology by the interprofessional team.

Objectives:

  • Review the mechanism physiology of electrophysiology study.
  • Identify important parameters measures in an electrophysiology study.
  • Outline the role and appropriate use of electrophysiology study in various cardiac pathologies.
  • Summarize how interprofessional collaboration can provide benefits and improved patient outcomes when using electrophysiology studies.

Introduction

Electrophysiology (EP) study is an invasive percutaneous cardiac procedure used for the investigation and treatment of certain arrhythmias. The aims of conducting an EP study are to access the function of each component of the conduction system, identify the mechanism and precise focus for arrhythmia, risk stratification and determine the need for treatment or therapy, including ablation of the aberrant circuit. This article presents an overview including anatomy and physiology, indications in common cardiac pathologies, and clinical significance of EP studies.

Anatomy and Physiology

Anatomy of the heart's conduction system comprises specialized cardiac muscle cells and conducting fibers (SA, AV nodes, HIS bundle, and Purkinje fibers) that conduct impulses through the heart and initiate the cardiac cycle and coordinate the synchronized contractions of the four cardiac chambers. EP study involves the placement of multipolar electrode catheters in the heart, typically in the right side, which generates intracardiac electrograms (EGMs) followed by programmed electrical stimulation (PES) to trigger a focus arrhythmia.

Intracardiac Electrograms (EGMs): These are electrical waves recorded by surface electrodes within the heart and represent local depolarization of the structures near the recording electrode. Hence, EGMs from the atrial (HRE) and ventricular(RVA/LV) catheters represent atrial and ventricular repolarization, respectively. EMGs from his bundle (HBE) represent atrial, his, and ventricular EMGs with the size of the atrial/ventricular component dependent on proximity to the respective structure. The carotid sinus (CS) involves both atrial and ventricular EGMs, atrial wave being larger in amplitude and ventricular waves smaller unless the catheter is advanced into the ventricular branch. Typical EP recordings include surface electrocardiograms, particularly of leads I, aVF, V1, and V6. The reader can orient themselves to tracings using the labels displayed along the left side of the margin and correlate the electrical activity with surface ECGs.

Lead position - Typical positions and their role is discussed here.

  1. The high right atrium (HRA) records the SA node electrical impulses. Pacing at this point allows assessment of SA node function, conduction from SA to AV node, and addition of premature complex or burst pacing through HRA may result in the induction of supraventricular tachyarrhythmia. Sinus node function is determined by SA nodal recovery time (SART) and SA nodal conduction time (SACT).
  2. Anterior tricuspid valve annulus (HBE) records electrical impulses that run through the bundle of his. This lead allows for the measurement of AH, HV, and His intervals, representing the AV node and ventricular conduction system.
  3. The right ventricle (RVA) records the ventricular apex. 
  4. Coronary sinus (CS 1-8) records left atrial activation as the coronary sinus runs in the mitral annulus.
  5. Left ventricle leads: This allows for LV mapping, particularly for evaluating left-sided SVTs or suspected left-sided accessory pathways.

Typical catheter positions and recordings during EP studies are represented in the diagram below. RA- right atrium, RV- Right ventricle, LA - left atrium, LV- Left ventricle.

Deflections in sinus rhythm: Normal atrial activation sequence in sinus rhythm is from HRA to low RA then concentrically from the CS (proximal to distal). The normal ventricular activation sequence is from RV apex and concentrically from CS (proximal to distal) 

Basic Electrophysiologic study of 5 distinct parts: measurement of baseline intervals, decremental ventricular pacing, decremental atrial pacing, atrial extra stimulus testing, and ventricular extra stimulus testing.

1. Baseline intervals:

  • Sinus cycle length: This is the interval between sinus atrial EGMs (A-A interval or P-P interval), surface PR, QRS, and QT intervals, representing the duration of the cardiac cycle.
  • Sinoatrial conduction time (SACT): this is a measure of sinus node function but lacks sensitivity for detecting sinus node dysfunction.
  • Sinoatrial nodal recovery time (SNRT): This is measured by placing catheter electrode near SA node and pacing for about 30s at a fixed rate that is faster than the intrinsic sinus rate, and the same process is repeated at progressively faster rates up to 200beats per minute then allow for recovery of the sinus node and restoration of intrinsic sinus conduction. The longest pause from the last pacing stimulus to the first intrinsic sinus beat represents the SNRT.
  • AH, interval (normal range 50 to 130 msec): This is measured on HBE as the time from first major deflection at baseline crossing to the onset of HIS bundle EMG and represents the conduction time through the AV node. The wide range in the normal subjects is due to the high concentration of muscarinic and adrenergic receptors on the AV node and influence with the autonomic nervous system. Short AH intervals represent fast conduction as seen due to increased sympathetic drive, steroid use, or pregnancy, while long AH intervals are seen with the parasympathetic drive (vagal tone) and with the use of AV blocking drugs (digoxin, Beta-blockers, calcium channel blockers, and antiarrhythmic drugs like amiodarone) 
  • His interval (normal range 10 to 25msec): This is measured on HBE as the beginning to the end of his deflection. It represents the conduction through a compact His bundle that penetrates through the fibrous septum.
  • HV interval (normal range 35 to 55 msec): This is measured on HBE as the interval from the onset of HIS to the onset of ventricular activation on any surface lead or intracardiac EGM and represents conduction through the His-Purkinje system. The autonomic system has an insignificant influence on this, and abnormalities usually reflect pathologic conduction defects. Symptomatic bradyarrhythmias and prolonged HV interval (> 55 ms)  or asymptomatic bradyarrhythmias with HV interval > 100msec indicate pacemaker therapy. Short HV interval represents either a ventricular preexcitation (i.e., AV bypass tract) or ventricular origin of beats (i.e., ventricular premature beats or accelerated idioventricular rhythm) 
  • VA conduction: This is assessed by ventricular extra stimulus and incremental ventricular pacing. The absence of VA conduction suggests the origin of arrhythmia above the AV node (atrial tachycardia) and makes AVNRT and AVRT less likely to focus. 
  • PA interval (normal range 20 to 60msec): This is measured from the earlier point on P wave on surface ECG to earlier deflection on intracardiac EGM.

2. Decremental ventricular pacing: This involves continuous pacing from the right ventricle apex with faster rates, i.e., shorter cycle lengths until AV block occurs. Here, current flows from the ventricle to atria allow for assessment of retrograde conduction through the AV node and allow for the identification of accessory pathways.

3. Decremental atrial pacing: This involves continuous pacing in the atria with progressively faster rates/shorter cycle lengths until AV block occurs. Here current flows from atria to ventricle, therefore, allows for assessment of anterograde conduction through the AV node and unmask alternative pathways or accessory tracks.

4. Atrial extra stimulus testing (AEST):  After baseline waves are recorded, multiple electrical impulses are administered at a fixed cycle length followed by a premature beat. The coupling interval of the premature beat is progressively shortened until the refractory period is reached. This allows for assessing the refractory period of anterograde AV node conduction and sometimes induces supraventricular and ventricular arrhythmias. Such programmed electrical stimulation of atria is used to determine the effective refractory period of the His-Purkinje system (usually < 450msec) 

5. Ventricular extra stimulus testing (VEST): This uses a similar technique of programmed electrical stimulation to assess the refractory period of retrograde AV node conduction

6. Mapping and Ablation: In many cases, the purpose of an EP study is diagnostic and therapeutic (i.e., ablation). Mapping refers to identifying the precise temporal and spatial distribution of electrical impulses generated by the myocardium and allows probing of the site where radiofrequency ablation can per performed for successfully curing the arrhythmia.

Indications

Rationale and indication for electrophysiologic studies in common cardiac pathologies are discussed here:

Sinus node dysfunction: Types of sinus node dysfunction:

  1. Sinus bradycardia
  2. Sinus arrest
  3. Sinoatrial block
  4. Sinus pause
  5. Chronotropic incompetence

EP studies have high specificity (75% to 95%) but low sensitivity of 50%.[1][2][3] Non-invasive methods like autonomic blockade and exercise stress test and diagnostic alternatives like implantable loop recorders are more accurate are less invasive tests with better sensitivity, which can help guide pacemaker placement and chose appropriate therapies. The use of EP studies is limited to niche indications.[2][4] EP studies do not help guide pacemaker implantation; therefore, they are not advisable in risk stratification of Sinus node dysfunction. Moreover, implantation of pacemakers in bradyarrhythmia has not been shown to improve long-term mortality.[5][6]

Class I indication:

In cases where non-invasive methods ( EKG, Holter monitor, or Loop recorders ) are inconclusive and cannot establish a relation of symptoms with bradyarrhythmia.

Class II indication:

In cases where the etiology of bradyarrhythmia is not clear, to differentiate intrinsic sinus node disease from effects of drugs or autonomic nervous system disease and select the appropriate therapeutic option.

To assess the inducibility of arrhythmia symptoms in documented sinus node dysfunction.

Class III indication:

1- Routine use before pacemaker implantation in syncope and documented asystole (>3 seconds) in whom association has already been established by non-invasive methods.

Acquired AV block: Recent studies suggest an improvement in mortality and symptoms in patients with complete atrioventricular block after a pacemaker placement.[7] AV blocks may be detected with routine EKGs or transient AV blocks with implantable loop recorders, and extrinsic causes for AV block are to be corrected (such as electrolyte disturbance: hyperkalemia, hypercalcemia, hypothyroidism, increased vagal tone: administration of negative dromotropic agents - beta-blockers, calcium channel blockers, digoxin or amiodarone.[8][9][10] Patients with 1st degree AV block do not need a pacemaker, while patients with more advanced AV conduction disorder Mobitz II, high-degree AV block, and complete AV block indicate pacemaker implantation irrespective of EP study. Therefore, the utility of EP studies is limited to cases where non-invasive studies fail to localize the site of block, primarily for Intrahisian and Infrahisian blocks.[11]

Class I indication:

None

Class II indication: 

In Mobitz type 2 AV block and second degree AV block with 2 to 1 AV block to determine the location of block (above or below the His bundle).[12]

Patients with paroxysmal AV block in patients with symptoms of syncope with no etiology found on non-invasive testing.[13]

In pseudo-AV block where concealed junctional depolarization are suspected of causing paroxysmal AV block.[14]

Class III Indications:

Prior to implanting a pacemaker for complete heart bock, high-degree AV block, and second-degree Mobitz type II AV block.

Isolated First degree AV block with no evidence of bundle branch block.

Asymptomatic patients with AV block due to increased vagal tone. 

Bundle branch block or intraventricular conduction delay: Patients with diseased His-Purkinje system, i.e., Bundle branch blocks or fascicular blocks  (QRS duration >120ms) or intraventricular conduction delay (QRS 100-120msec) are at risk of progression to complete AV block. Such patients at risk of progression may benefit from Pacemaker implantation. EP studies can identify these patients at high risk of progression and therefore is used for risk stratification in patients presenting with syncope with bundle branch block on EKG.[15] The positive predictive value of EP study in determining patients who require PM implantation is > 80%.[16] Important aspects of evaluating the remaining fibers of the conduction system are the HV interval, incremental atrial pacing, and pharmacologic provocation with Class IA/Class IC antiarrhythmic drugs. Studies show a progression to complete AV block at 4 years was <4% for HV interval of < 70ms, 12% for HV interval of 70-100ms and 24% for HV > 100ms. Therefore PM implantation is recommended in patients with syncope with BBB and HV for > 70ms. Similarly, the development of an AV block during incremental atrial pacing and the pharmacologic blockage is predictive of a high risk of progression to complete block. 

Class I indication:

Risk stratification of the patient with unexplained syncope with bifasicular block on EKG

Class II indication:

Asymptomatic patients with bundle branch blocks in whom pharmacologic therapy with AV blocking drugs is being considered for another indication

A complete EP study to identify the cause of unexplained syncope in patients with intraventricular conduction delay.

Class III indication:

Assymtpnatic patients were found to have intraventricular conduction delay or incomplete BBB with QRS <120s.

Symptomatic patients with BBB where symptoms can be correlated with or excluded by ECG events

Indications for pharmacologic provocation during EP study: Symptomatic patients with HV interval 35 - 69ms. No role in asymptomatic patients with IVCD or BBBs.

Narrow QRS complex tachycardia: The SVTs are a group of arrhythmias with QRS <120ms with HR > 100bmp and comprise of sinus tachycardia, multifocal and focal atrial tachycardia, Atrioventricular nodal reentry tachycardia (AVNRT), atrioventricular reentrant tachycardia (AVRT), atrial flutter, and focal junctional tachycardia (FJT). The diagnosis of SVTs is not always possible by non-invasive methods, and an EP study may identify the mechanism of tachycardia and guide catheter ablation for definitive treatment. Ablation is the treatment of choice for AVNT compared to antiarrhythmic drugs, which are less effective and poorly tolerated.[17]

Class I indication:

Patients with poorly tolerated tachycardia episodes with inadequate response to drug therapy and for whom the site of origin, mechanism, and EP properties of the pathways is essential for choosing appropriate therapy.

Class II indication:

Patients who prefer ablative therapy over antiarrhythmic drug therapy.

Class II indication:

Patients with well-controlled symptoms with vagal maneuvers or well-tolerated drug therapy where ablation is not indicated.

Wide QRS complex tachycardia: These are characterized by QRS >120ms and include 3 distinct entities ventricular tachycardia, Supraventricular tachycardia with pre-existing functional bundle branch block, and ventricular preexcitation. Ventricular tachycardia includes isolated premature ventricular complexes (PVCs), ventricular couplets, non-sustained and sustained ventricular tachycardia, and preexcitation (WPW).

a) Indications for EP study in patients with PVS, couplets, and NSVT:  Studies show that risk of sudden death is related to frequency and complexity of PVCs, couplets, NSVT and is worse in patients with underlying structural heart disease. Post MI, complex (Lown class 4 or 5) and frequent >10 PVCs per hour represent higher mortality risk.[18] The MUSTT trial revealed candidates with a prior MI, HRrEF (EF <40%), and nonsustained VT. EPS strongly guided therapeutic strategy and select candidates suitable for ICD implantation. EP study is useful in risk stratification for PVCs in cases of high arrhythmic burden or tachycardiomyopathy due to frequent PVCs. Therefore, the EP study helps 1) establish the mechanism of underlying tachycardia in doubtful cases, 2) identify patients at risk of sudden cardiac death and identify patients eligible for ICD implantation 3) Guide catheter ablation.[19][20]

Class I indication:

None

Class II indication:

Patients with risk factors for future arrhythmic events - i.e., reduced EF, positive signal-averaged ECG, and NSVT on ambulatory ECG recordings EPS is used for risk stratification and guide therapy (i.e., medication vs. ICD implantation) in patients with inducible VTs.

Patients with symptomatic PVCs, couplets, and NSVT who can be potential candidates for catheter ablation.[14]

In patients with prior MI, low EF with non-sustained VT, the use of EPS for programmed ventricular stimulation is indicated for the selection of patients suitable for ICD implantation.[21]

Class III indications:

Asymptomatic or mild symptoms in patients with PVCs, couplets, or NSVT without risk factors for arrhythmias.

b) Indications for EP study in sustained monomorphic ventricular tachycardia (MVT): The presence of MVT in structural heart disease indicates ICD placement. EP studies are used in patients with MVT in structurally normal hearts to identify patients who will benefit from catheter ablation. Even in patients who meet the criteria for catheter ablation, programmed electrical stimulation precedes the procedure. 

Class I indication:

Before ablation for patients with symptomatic MVT with EKG findings suggestive of RVOT tachyarrhythmia in the absence of structural heart disease.

Prior to catheter ablation with MVT.

Patients with wide QRS tachycardia where the diagnosis is unclear after ECG analysis where knowledge of correct diagnosis has implications in determining appropriate therapy.[14]

Class II indication

Patients who do not want long-term anti-arrhythmic drugs or failure of Class IC agents before catheter ablation of LVOT/epicardial VT/aortic cusp/PVC. 

Patients with VT following recent valve surgery to identify and cure bundle branch re-entry VT

Class III indications

Patients with VT/SVT with aberrant conduction or pre-excitation syndrome where the diagnosis is clear with ECG analysis and invasive EP data will not influence therapy. 

c) Indications of EP study in polymorphic ventricular tachycardia (PVT): PVTs usually occur in the context of acute MI, preceding sinus pauses, prolonged QT interval, electrolyte disturbance, sinus bradycardia, or catecholaminergic PVT where exercise or intense emotion trigger the arrhythmia.  There is no indication for EP studies in PVTs.

d) Indications of EP study in pre-excitation syndromes: Patients with symptomatic WPW (palpitations, syncope, dyspnea, chest pain, sudden death post-resuscitation) benefit from EP study and catheter ablation. If the accessory pathway has a refractory period  < 240ms, catheter ablation is the first-line therapeutic option.[22] Asymptomatic patients with WPW have a lower risk of SCD, but SCD may be the first symptom for patients with asymptomatic EKG findings. Therefore the use of EP study is important for risk stratification in these patients. 

Class I indications: 

Patients with ventricular pre-excitation post CPR who survived cardiac arrest or who had unexplained syncope. 

Patients with SVT where etiology is not clear for the identification of WPW and possible catheter ablation.

Class II indications:

Patients with asymptomatic EKG findings of pre-excitation syndrome for risk stratification.

Asymptomatic patients where EP study demonstrates high-risk features, it is reasonable to perform catheter ablation of the accessory pathway.

Asymptomatic patients with pre-excitation and high-risk professions (such as pilot, surgeon, drivers) for catheter ablation.

Class III indications:

None

Inherited primary arrhythmia syndromes (Channelopathies) 

Long QT syndrome (LQTS): The risk of sudden cardiac death (SCD) in Long QT syndrome depends on age, sex, and QTc interval duration and ranges from 15 to 70%.[23] Therefore, it is important to identify patients at high risk for SCD. A 12 lead EKG is a very useful risk stratification tool in these patients and QTc> 500ms and presence of T-wave alternans is a useful marker of electrical instability.  Studies show that patients with QT syndrome who have had a previous syncope episode may not elicit VT on programmed electrical stimulation of EP study. Rapid polymorphic VT may be induced in 40% of the patients with the protocol using 3 extra stimuli with and without isoprenaline administration. Moreover, the presence of NSVT has no prognostic value in identifying high-risk patients for future SCD. Therefore, an EP study is not indicated in long QT syndrome. Per ESC Guidelines 2015, the use of EPS is a class III, LOE C for evaluation of patients with LQTS. 

Short QT syndrome (SQTS): These are congenital channelopathies with QTc <330ms associated with an increased risk of malignant ventricular arrhythmias leading to cardiac arrest. Early identification of high-risk patients and ICD implantation is important for secondary prevention of sudden cardiac death in these patients. EPS has low sensitivity (37%) for the detection of high-risk patients, but the negative predictive value is still modest at 58%.[24] Based on these studies, per the 2015 ESC guidelines use of EP study have Class III, LOE C in the evaluation of SQTS.  

Brugada Syndrome ( BrS): This is an inherited arrhythmogenic pathology with a unique ECG appearance (ST-elevation of > 2mm in the right precordial leads V1 and V2 positioned in the 2nd, 3rd, or 4th intercostal space) and a tendency to develop syncope or cardiac arrest from VT either spontaneously or with use of provocative drugs (Class I drugs - ajmaline, pilsicainide, procainamide, or flecainide). Multiple clinical trials on the use of EP studies in risk stratification have had mixed results. Therefore there is yet no consensus about the value of EPS in Brugada syndrome.[25][26][27][28][29][30][31] Patients with a history of CA are candidates for ICD implantation regardless of EP study findings. Patients without symptoms or syncope may benefit from EPS study, and 2015 ESC guidelines have given a Class IIb or LOE C recommendation for ICD implantation in patients who develop VT during EP study - programmed ventricular stimulation with 2-3 extra stimuli at two sites. 

Class I indication

None

Class II indication

EPS has no role in risk stratification in patients with BrS with CA or spontaneous VT or VT and spontaneous type 1 Brugada pattern. In other cases, the EP study is used in the case by case basis for risk stratification and determining eligibility for ICD implantation.

In BrS and inductive VF, EP testing may be used as an alternative to ICD therapy to assess treatment efficacy.

Class III indication

For routine risk stratification in patients with asymptomatic type 2 BrS. 

Catecholaminergic Polymorphic VT (CPVT): Rare genetic conduction disease associated with polymorphic or bidirectional VT during the adrenergic surge (physical or emotional stimulation or stressful situation) in the absence of structural heart disease, or QT prolongation, which can cause sudden cardiac death or syncope. Diagnosis and risk stratification are based on the exercise stress test, Holter monitor, or ILRs combined with genetic testing. The presence of syncope is not a reliable predictive marker.[32] There are no large randomized controlled clinical trials assessing the role of EPS in risk stratification for these patients thus far, but according to the 2015 ESC guidelines for managing patients with ventricular arrhythmias, EPS has been established as a Class III indication for evaluation of CPVT.

Progressive cardiac conduction disease (PCCD): This is a rare genetic cardiac conduction disease associated with SCN5A gene mutation. The common form is known as “Lenègre–Lev disease.” The disease presents in young individuals, usually under 50 years, with the absence of skeletal myopathies and structurally normal hearts with a wide degree of conduction abnormalities, including first-degree AV block to third-degree AV block. These patients are at high risk of SCD, and EP studies have a crucial role in diagnosis and risk stratification. Patients with third-degree AVB, bifascicular block with infranodal first-degree AVB are suitable candidates for pacemaker implantation without prior EP studies. 

Early depolarization syndrome: This is associated with a high risk of idiopathic VF. Studies that performed PVS in these patients with a history of VF revealed the VF was inducible only in 22% of the patients at risk.[33] Therefore until further evidence emerges, EPS is believed to have low diagnostic accuracy and no role in risk stratification for VT in these patients.

Inherited structural heart diseases:

Hypertrophic cardiomyopathy (HCM) - Inherited HCM is associated with SVTs and VTs, which may lead to sudden cardiac death. Moreover, due to the presence of structural heart disease, medications such as Class IA and IC medications are contraindicated, and the therapeutic options are limited to ICD, PM implantation, or catheter ablation. Patients with VF or sustained VT require ICD implantation. Based on previous studies, EP studies had low sensitivity for VT induction on PVS, but a recently published report by Gatzoulis et al. reported that use of one non-invasive risk factor for SCD in addition to inducible VT during PVS and AHA indication or ICD or an ESC score of > 6% has 100% sensitivity and negative predictive value for identification of patients with high and low risk of SCD and appropriate ICD placement.[34][35][36]

Class I indications:[37]

Patients with recurrent SVT to determine the precise location and etiology of arrhythmia and possible catheter ablation in certain cases.

Class II indications:

Patients with symptomatic, sustained (> 30s) VT who are candidates for catheter ablation.

Class III

EPS with PVS is not recommended for sudden cardiac death risk stratification, although this may change based on new emerging data. 

Dilated cardiomyopathy (DCM) - Nearly 70% of DCM patients demonstrate NSVT on Holter monitor, and the incidence of sudden death is 30 to 40% in patients with DCM. Patients with DCM commonly have ventricular arrhythmias - PVCs, NSVT, sustained monomorphic VT and polymorphic VT, less commonly atrial or supraventricular arrhythmias AF, AFl, and AT. Traditionally risk stratification of SCD is performed by LVEF measurement, but this marker fails to have low NPV and low specificity. Patients with sustained monomorphic VT or VF require ICD implantation, and EPS is not necessary. The role of EP study in all other patients with DCM is for risk stratification and SVT/VT diagnosis that is amenable to catheter ablation. 

Class I indications

None

Class II indications

Invasive EPS with PVS for risk stratification for SCD

Patients with sustained monomorphic VT to guide catheter ablation.

Arrhythmogenic right ventricular cardiomyopathy (ARVC): Patients with ARVC are at high risk of malignant arrhythmias and SCD. These patients are categorized into subgroups based on clinical presentation.

ARVC and aborted cardiac arrest or VT with a hemodynamic compromise - This is a class I indication for ICD placement, and EP study has no role in guiding therapy or risk stratification. 

ARVC with hemodynamically stable monomorphic tachycardia - Patients with spontaneously induced VT have class IIa indication for ICD implantation. Inducible VT on EPS may be a predictor of adverse outcomes (syncope, SCD, heart transplantation, VT, and VF with hemodynamic compromise) and can be an independent predictor of ICD implantation. The use of EP study does not give additional information compared to follow-up VTs. Therefore, it is a futile investigation unless coupled with the electro-anatomical mapping of the diseased myocardium and radiofrequency ablation. 

ARVC with wide-complex QRS tachycardia with LBBB morphology - VT or SVT with aberrant conduction/pre-excitation when 12 lead EKG does not help make the differential diagnosis, EPS may be useful for identification of the focus and possible therapeutic intervention.

ARVC with symptoms suggestive of malignant arrhythmia but no documented history of sustained monomorphic VT: If patients have no evidence of VT on non-invasive testing - EKG, Holter monitor, or ILRs, presence of inducible VT during PVS is an indication of ICD placement.

Left ventricular noncompaction (LVNC): These patients are at high risk of malignant arrhythmias, and there are no specific EKG findings predictive of VT inducibility. There are few relevant studies aimed at risk stratification using EPS in these patients. The decision for ICD placement in these patients is based on LVEF and the presence of malignant VTs. EPS has no role in these patients.

Muscular dystrophies: Duchene muscular dystrophy and Becker muscular dystrophy are characterized by a variable degree of muscular weakness, rhabdomyolysis, and cardiomyopathy. Cardiomyopathy is characterized by myocardial fibrosis, diastolic and systolic dysfunction, and conduction disorders. Approximately 25% of patients with BMD have cardiomyopathy at age 6, while the incidence increases to 60% by the age of 10 years. Subsequently, the prevalence of SCD is significant in these patients, mostly due to paroxysmal AV block, less commonly due to malignant VT. Therefore, routine Holter monitoring is recommended.[38][39] EP studies may be used to identify patients with high degree conduction disease and guide pacemaker implantation.

Class I indications:

None

Class II indications:

Patients with myotonic dystrophy in the absence of conduction disease on EKG to identify patients with increased risk of AV block ( Patients with HV interval > 70ms benefit from PM implantation)

Acquired Structural Heart Disease

1- Ischemic heart disease: This is a significant cause of SCD, but only a small fraction of patients with IHD will have a malignant arrhythmia, higher risk in acute coronary syndromes, and lower in stable CAD. EP study plays an important role in risk stratification and identification of patients at high risk of ventricular arrhythmias, asses indications for ICD therapy and catheter ablation.

Stable coronary artery disease in the absence of myocardial infarction: These patients are at lower risk for arrhythmia and do not need EPS routinely unless clinical features suggest concomitant conduction disorder. 

Within the first 48 hours of MI, acute coronary syndrome: These patients are at risk of VT/VF in the acute phase and need close monitoring with non-invasive methods during this phase. EPs study is not indicated in this phase as the arrhythmias occurring during this phase do not necessarily correlate with future events, and correcting acute ischemia is more important.[40]

Post-Myocardial infarction (MI):

Acute phase - 48 hours to 40 days: During this phase, in addition to LVEF, EPS is the only method tested in randomized clinical trials to guide ICD implantation in early, subacute, and remote phases after MI. The data regarding EPS to guide ICD implantation is conflicting multiple trials - DINAMIT, IRIS, BEST-ICD have failed to show an overall mortality benefit in subgroups with EPS guided ICD implantation. Weastmed EPS/ICD observational studies and MUSTT trial show a survival benefit in EPS guided ICD implantation. Overall, based on these studies, patients with LVEF <40% and negative EPS are at low risk of arrhythmia and SCD. Positive EPS correlates with future risk of arrhythmias and should be a consideration in ICD implantation.[41][42][43]

Subacute phase after MI 40 days to 6 months: Date regarding EPS during this phase is more congruent and largely favor EP study for identification of patients at high risk of ventricular arrhythmia recurrence [Alternans Before Cardioverter Defibrillator (ABCD) and Cardiac arrhythmias and risk stratification after acute MI (CRISMA) trials]

Remote phase post-MI (>6 months): In patients with severe LV dysfunction (LVEF < 30%), implantation of ICD offers survival benefits regardless of EP study, and therefore the role of EP study in these patients is limited. For patients with moderately low LVEF (30 to 40%) with non-sustained VT, an EPS guided strategy to select suitable candidates results in at least 31% mortality reduction,[44]

Postantiarryhythmic surgery: 2015 ESC guidelines recommend intraoperative EP mapping and catheter or surgical ablation in experienced centers (Class IIb indication), and surgical ablation is preferred in patients undergoing surgery for another indication, e.g., CABG or valve surgery. The use of an ICD is considered in other patients, and EPS is beneficial in patients who underwent antiarrhythmic surgery to test for the inducibility of VT and identify potential candidates for ICD implantation.

Class I indications

EPS in CAD for the diagnostic evaluation of remote MI with symptoms suggestive of malignant ventricular arrhythmias (syncope, pre-syncope, and palpitations)

Class II indications

For patients with previous MI and BBB, EPS with PES is advisable to identify ICD implantation candidates.

Survivors of MI with preserved LVEF presenting with unexplained syncope

Patients with MI, LVEF < 40%, and NSVT for selection of candidates for ICD implantation

Patients who underwent antiarrhythmic surgery for follow-up in 2 weeks to 6 months to evaluate the result of surgery and select candidates for ICD implantation.

Infiltrative Disease: 

Amyloidosis: Conduction disorders sometimes complicate amyloidosis, and EPS can identify patients who need pacemaker implantation. Data is limited to case reports, and the largest study by Reisinger et al., which includes subjects, was 25 biopsy-proven AL amyloidosis patients with cardiac involvement, and their electrophysiological abnormalities were studied by an EP study correlated with the risk of sudden cardiac death. Study results were analyzed using multivariate analysis, which revealed that a prolonged HV interval was the only independent predictor of sudden death (p < 0.05), suggesting the role of EPS in guiding PM implantation.[45]

Sarcoidosis: Cardiac sarcoidosis is complicated by ventricular arrhythmias presenting as syncope or sudden cardiac death due to macro-reentry circuits. EP studies help identify patients at risk of ventricular arrhythmias and guide catheter ablation, usually in combination with anti-arrhythmic medications. Asymptomatic patients may also benefit from EP studies as SCD may be the first manifestation of cardiac involvement in sarcoidosis. EP study positive for inducible VT on PES is predictive for future risk of SCD.[46]

Class I indications:

None

Class II indications:

Sarcoidosis patients with syncope of suspected arrhythmic etiology

Mapping and precise localization of VT and possible catheter ablation in patients with documented VT due to cardiac sarcoidosis

Congenital heart disease (CHD): It is believed that nearly half of 20-year-old patients with CHD will develop an atrial tachyarrhythmia during their lifetime, although the prevalence of ventricular arrhythmias may vary based on the type and severity of CHD. Nearly 1% to 2% of patients with tetralogy of fallout (ToF) develop VTs over 5 years. Valvular aortic stenosis, pulmonary stenosis, and ventricular septal defects are associated with isolated PVCs. The annual incidence of SCD is 0.09% per year in all patients with CHD, largely driven by malignant VTs, and identification of high-risk patients with subsequent ICD implantation is associated with a significant reduction in mortality in these patients.[47]

The role of EP studies in CHD is to 1- evaluate the cause of unexplained syncope, 2-establish prognosis, 3-mapping and possible intervention such as catheter ablation, 4-identify patients who are eligible for device implantation.

Class I indications:

Unexplained syncope in patients with high-risk CHD (tetralogy of Fallot, transposition of great vessels, or single ventricular dysfunction)

CHD patient with spontaneous sustained VT for possible catheter ablation

Class IIa indications:

CHD with life-threatening arrhythmias or post-resuscitation after cardiac arrest where the proximate cause for the event is unknown or unclear, PES may identify the focus of arrhythmia and guide therapeutic intervention

PVS is useful for patients with ToF with high-risk features - systolic or ventricular dysfunction, NSVT, prolonged QRS (> 180ms), and extreme RV scarring.

Unexplained syncope and impaired LV function in CHD patients with other workup have been unrevealing, and ICD placement is reasonable. 

Patients with CHD and documented SVT and ventricular pre-excitation.

Class IIb indication:

CHD patient with palpitations where conventional workup has been unrevealing

CHD patients with ventricular couplets or NSVT to determine the risk of subsequent VT.

Class III indication: 

PVS is not indicated for routine screening and risk stratification of ToF patients.

PVS does not appear to benefit patients with transposition of great vessels in the absence of symptoms.

Unexplained syncope

First-line diagnostic tools for workup for syncope of suspected cardiac etiology is the 12 lead EKG, Holter monitor, or implantable loop recorder depending on the frequency of symptoms. The purpose of EPS is mainly to identify the etiology of syncope in suspected intermittent bradycardia or tachycardia or BBB, and the diagnostic yield is better in patients with prior structural heart disease or an abnormal EKG. Patients with inducible VT with PES are at high risk for subsequent VTs and carry a poor prognosis.

Class I indication:

Patients with ischemic heart disease with syncope evaluation in patients who do not have an indication for ICD implantation.

For patients with unexplained syncope with bifasicular block, EPS has high sensitivity in identifying patients with impending high-degree AV block.

Class II a indications:

None

Class II b indications:

Patients with syncope are preceded by palpitations where non-invasive tests have failed to identify a diagnosis.

Patients with BrS, ARVC, and HCM for select cases.

Patients with high-risk occupations where every effort to exclude cardiac syncope is warranted.

Class III indication:

EPS is not indicated in patients with structurally normal hearts with normal EKG and no palpitations.

There are the EP study diagnostic findings suggestive of cardiogenic syncope:

  • Sinus bradycardia – CSNRT > 525 ms
  • Induction of sustained monomorphic VT in patients with prior MI
  • BBB and baseline HV > 100ms or second- or third-degree block demonstrated during incremental atrial pacing or pharmacologic challenge.
  • An HV interval between 70-100ms.
  • Induction of rapid SVT with hemodynamic compromise.
  • Induction of polymorphic VT in ischemic cardiomyopathy, BrS, HCM, ARVC, or DCM.

Contraindications

Absolute contraindications for an electrophysiology study are:

  • Bloodstream infection or sepsis
  • Acute decompensation heart failure that is not precipitated by an arrhythmia, as this may induce an arrhythmia
  • Risk of Major bleeding (E.g. supratherapeutic INR, DIC)
  • Local infection or thrombosis of access site vessel ( femoral DVT or lower limb cellulitis)

Complications

These are similar to any percutaneous procedure including the risk of vessel damage, hemorrhage requiring transfusion therapy, sepsis from catheter side access, MI, stroke, and death due to hypoperfusion and related complications. As EP study involves the placement of multiple electrodes at different points, it carries a risk of damage to important structures including the tricuspid valve and cardiac chamber perforation leading to cardiac tamponade and death.

Clinical Significance

An electrophysiology study can be used for risk stratification as well as diagnosis of conduction disorders.

Diagnostic Indications

a) Unexplained syncope without any conduction disturbance or in patients with ischemic heart disease, sinus node dysfunction or sinus bradycardia, bifascicular block, or patients with palpitations or high-risk occupations (driving, air traffic controller, pilots, etc.)

b) Wide complex tachycardia where non-invasive testing shows equivocal results

c) Cardiac arrest survivors as part of the diagnostic workup 

Risk Stratification Indications

a) Primary prevention of sudden cardiac death in patients with ischemic heart disease, AV conduction abnormalities, asymptomatic young patients with pre-excitation syndromes, congenital cardiac disorders ( ToF, BrS, ARVC), and acquired disorders (sarcoidosis and amyloidosis).

Enhancing Healthcare Team Outcomes

The field of electrophysiology has greatly developed in the past decades. As a result, the use of EP studies in clinical practice has significantly enhanced. EP studies are still an invasive test with limited utility in certain niche indications, whereas it can provide practice-changing information in some arrhythmias. It is therefore imperative that clinicians understand the importance and role of EP studies in various cardiac pathologies and refer patients for this invasive study judiciously in line with the principles of high-value care.


Article Details

Article Author

Hafsa Majeed

Article Editor:

Yasar Sattar

Updated:

10/11/2021 10:57:23 AM

References

[1]

Benditt DG,Gornick CC,Dunbar D,Almquist A,Pool-Schneider S, Indications for electrophysiologic testing in the diagnosis and assessment of sinus node dysfunction. Circulation. 1987 Apr     [PubMed PMID: 3549054]

[2]

Maisch B,Lotze U,Schneider J,Kochsiek K, Antibodies to human sinus node in sick sinus syndrome. Pacing and clinical electrophysiology : PACE. 1986 Nov     [PubMed PMID: 2432516]

[3]

Fujimura O,Yee R,Klein GJ,Sharma AD,Boahene KA, The diagnostic sensitivity of electrophysiologic testing in patients with syncope caused by transient bradycardia. The New England journal of medicine. 1989 Dec 21     [PubMed PMID: 2594030]

[4]

Midwifery teacher training workshop., Duff G,, The New Zealand nursing journal. Kai tiaki, 1978 Jun     [PubMed PMID: 23801827]

[5]

NZNA submission on confidentiality of health computer., , The New Zealand nursing journal. Kai tiaki, 1978 Jun     [PubMed PMID: 9236443]

[6]

Coming to terms with cancer., Davidson GP,, The New Zealand nursing journal. Kai tiaki, 1978 Jun     [PubMed PMID: 2432517]

[7]

Planned animal health and production service--P.A.H.A.P.S., Moller K,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 9272517]

[8]

Brignole M,Guieu R,Tomaino M,Iori M,Ungar A,Bertolone C,Unterhuber M,Bottoni N,Tesi F,Claude Deharo J, Mechanism of syncope without prodromes with normal heart and normal electrocardiogram. Heart rhythm. 2017 Feb     [PubMed PMID: 27639455]

[9]

Maggi R,Rafanelli M,Ceccofiglio A,Solari D,Brignole M,Ungar A, Additional diagnostic value of implantable loop recorder in patients with initial diagnosis of real or apparent transient loss of consciousness of uncertain origin. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2014 Aug     [PubMed PMID: 24668513]

[10]

Krahn AD,Morillo CA,Kus T,Manns B,Rose S,Brignole M,Sheldon RS, Empiric pacemaker compared with a monitoring strategy in patients with syncope and bifascicular conduction block--rationale and design of the Syncope: Pacing or Recording in ThE Later Years (SPRITELY) study. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2012 Jul     [PubMed PMID: 22318881]

[11]

Toxicity of zinc in ruminants in relation to facial eczema., Smith BL,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 7064840]

[12]

Research and the rural veterinarian., Joyce G,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 23265327]

[13]

Steroidal and non-steroidal anti-inflammatory drugs for wounds and traumatic inflammation., Jones EW,Hamm D,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 29255501]

[14]

Anaesthesia of swine., Anderson IL,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 8535564]

[15]

Scheinman MM,Peters RW,Suavé MJ,Desai J,Abbott JA,Cogan J,Wohl B,Williams K, Value of the H-Q interval in patients with bundle branch block and the role of prophylactic permanent pacing. The American journal of cardiology. 1982 Dec     [PubMed PMID: 7148708]

[16]

Brignole M,Auricchio A,Baron-Esquivias G,Bordachar P,Boriani G,Breithardt OA,Cleland J,Deharo JC,Delgado V,Elliott PM,Gorenek B,Israel CW,Leclercq C,Linde C,Mont L,Padeletti L,Sutton R,Vardas PE, 2013 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy. Revista espanola de cardiologia (English ed.). 2014 Jan     [PubMed PMID: 24774265]

[17]

Katritsis DG,Zografos T,Katritsis GD,Giazitzoglou E,Vachliotis V,Paxinos G,Camm AJ,Josephson ME, Catheter ablation vs. antiarrhythmic drug therapy in patients with symptomatic atrioventricular nodal re-entrant tachycardia: a randomized, controlled trial. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2017 Apr 1     [PubMed PMID: 28431060]

[18]

Pasture management on Waikato equine studs., Wallace T,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 2870632]

[19]

The need for research in small animal medicine., Busch TJ,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 29414264]

[20]

Isolation of leptospires from the vitreous humor of aborted piglets., Ryan TJ,Marshall RB,Edwards JD,Stevenson BJ,, New Zealand veterinary journal, 1977 Nov     [PubMed PMID: 6486025]

[21]

Buxton AE,Lee KL,DiCarlo L,Gold MR,Greer GS,Prystowsky EN,O'Toole MF,Tang A,Fisher JD,Coromilas J,Talajic M,Hafley G, Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. The New England journal of medicine. 2000 Jun 29     [PubMed PMID: 10874061]

[22]

Page RL,Joglar JA,Caldwell MA,Calkins H,Conti JB,Deal BJ,Estes NAM 3rd,Field ME,Goldberger ZD,Hammill SC,Indik JH,Lindsay BD,Olshansky B,Russo AM,Shen WK,Tracy CM,Al-Khatib SM, 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology. 2016 Apr 5;     [PubMed PMID: 26409259]

[23]

Goldenberg I,Zareba W,Moss AJ, Long QT Syndrome. Current problems in cardiology. 2008 Nov     [PubMed PMID: 18835466]

[24]

Giustetto C,Schimpf R,Mazzanti A,Scrocco C,Maury P,Anttonen O,Probst V,Blanc JJ,Sbragia P,Dalmasso P,Borggrefe M,Gaita F, Long-term follow-up of patients with short QT syndrome. Journal of the American College of Cardiology. 2011 Aug 2     [PubMed PMID: 21798421]

[25]

Oestrus synchronisation with a prostaglandin analogue: I. Systems in lactating dairy cattle., Macmillan KL,Curnow RJ,Morris GR,, New Zealand veterinary journal, 1977 Dec     [PubMed PMID: 22920782]

[26]

The lightcast system of limb immobilisation., Horney FD,, New Zealand veterinary journal, 1977 Dec     [PubMed PMID: 19193676]

[27]

Delise P,Allocca G,Marras E,Giustetto C,Gaita F,Sciarra L,Calo L,Proclemer A,Marziali M,Rebellato L,Berton G,Coro L,Sitta N, Risk stratification in individuals with the Brugada type 1 ECG pattern without previous cardiac arrest: usefulness of a combined clinical and electrophysiologic approach. European heart journal. 2011 Jan     [PubMed PMID: 20978016]

[28]

Brugada P,Brugada R,Mont L,Rivero M,Geelen P,Brugada J, Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart. Journal of cardiovascular electrophysiology. 2003 May     [PubMed PMID: 12776858]

[29]

Brugada J,Brugada R,Brugada P, Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation. 2003 Dec 23     [PubMed PMID: 14623800]

[30]

Veterinary examination for three-day-events., Oulaghan KA,, New Zealand veterinary journal, 1977 Dec     [PubMed PMID: 20100972]

[31]

Endurance riding and "scoring" endurance rides., Kelly CM,, New Zealand veterinary journal, 1977 Dec     [PubMed PMID: 22192666]

[32]

Priori SG,Wilde AA,Horie M,Cho Y,Behr ER,Berul C,Blom N,Brugada J,Chiang CE,Huikuri H,Kannankeril P,Krahn A,Leenhardt A,Moss A,Schwartz PJ,Shimizu W,Tomaselli G,Tracy C, HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart rhythm. 2013 Dec;     [PubMed PMID: 24011539]

[33]

Flock treatment of some poultry diseases., Tempest CH,, New Zealand veterinary journal, 1977 Dec     [PubMed PMID: 25593056]

[34]

Scrapie-a point of view., Bruere AN,, New Zealand veterinary journal, 1977 Dec     [PubMed PMID: 25553935]

[35]

Priori SG,Blomström-Lundqvist C,Mazzanti A,Blom N,Borggrefe M,Camm J,Elliott PM,Fitzsimons D,Hatala R,Hindricks G,Kirchhof P,Kjeldsen K,Kuck KH,Hernandez-Madrid A,Nikolaou N,Norekvål TM,Spaulding C,Van Veldhuisen DJ, [2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac Death. The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology]. Giornale italiano di cardiologia (2006). 2016 Feb     [PubMed PMID: 27029760]

[36]

Gatzoulis KA,Georgopoulos S,Antoniou CK,Anastasakis A,Dilaveris P,Arsenos P,Sideris S,Tsiachris D,Archontakis S,Sotiropoulos E,Theopistou A,Skiadas I,Kallikazaros I,Stefanadis C,Tousoulis D, Programmed ventricular stimulation predicts arrhythmic events and survival in hypertrophic cardiomyopathy. International journal of cardiology. 2018 Mar 1     [PubMed PMID: 29407088]

[37]

Elliott PM,Anastasakis A,Borger MA,Borggrefe M,Cecchi F,Charron P,Hagege AA,Lafont A,Limongelli G,Mahrholdt H,McKenna WJ,Mogensen J,Nihoyannopoulos P,Nistri S,Pieper PG,Pieske B,Rapezzi C,Rutten FH,Tillmanns C,Watkins H, 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). European heart journal. 2014 Oct 14     [PubMed PMID: 25173338]

[38]

Subsidies and rural practice., Horney FD,, New Zealand veterinary journal, 1978 Jan-Feb     [PubMed PMID: 11909570]

[39]

The effect of mebendazole and praziquantel on the cysts of Echinococcus granulosus, Taenia hydatigena and T. ovis in sheep., Heath DD,Lawrence SB,, New Zealand veterinary journal, 1978 Jan-Feb     [PubMed PMID: 12875769]

[40]

Bovine photosensitization in New Zealand., Smith BL,O'Hara PJ,, New Zealand veterinary journal, 1978 Jan-Feb     [PubMed PMID: 19417195]

[41]

Evaluation of herd and flock health programmes., Harris RE,, New Zealand veterinary journal, 1978 Jan-Feb     [PubMed PMID: 15590950]

[42]

Steinbeck G,Andresen D,Seidl K,Brachmann J,Hoffmann E,Wojciechowski D,Kornacewicz-Jach Z,Sredniawa B,Lupkovics G,Hofgärtner F,Lubinski A,Rosenqvist M,Habets A,Wegscheider K,Senges J, Defibrillator implantation early after myocardial infarction. The New England journal of medicine. 2009 Oct 8     [PubMed PMID: 19812399]

[43]

Raviele A,Bongiorni MG,Brignole M,Cappato R,Capucci A,Gaita F,Gulizia M,Mangiameli S,Montenero AS,Pedretti RF,Uriarte JA,Sermasi S,Nisam S, Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2005 Jul     [PubMed PMID: 16028343]

[44]

Piccini JP,Hafley GE,Lee KL,Fisher JD,Josephson ME,Prystowsky EN,Buxton AE, Mode of induction of ventricular tachycardia and prognosis in patients with coronary disease: the Multicenter UnSustained Tachycardia Trial (MUSTT). Journal of cardiovascular electrophysiology. 2009 Aug     [PubMed PMID: 19490266]

[45]

CFT inaccurate for epididymitis., Hicks JD,Burr GR,Marshall DR,Vidler BM,, New Zealand veterinary journal, 1978 Jan-Feb     [PubMed PMID: 9316537]

[46]

Short returns in ewes synchronised with prostaglandins., Allison AJ,, New Zealand veterinary journal, 1978 Jan-Feb     [PubMed PMID: 21193539]

[47]

Factors associated with wounds and bruises in lambs., Petersen GV,, New Zealand veterinary journal, 1978 Jan-Feb     [PubMed PMID: 22991410]